Overview

Population Characteristics

  • This dataset include 62 confirmed cases admitted from 2018-08-05 to 2019-05-13.

  • 55% girls and 29% children ≤5 years .

  • 20 confirmed deaths reported for an average CFR of 32%.

Stratified Tables

Population characteristics: Children va Adults
Characteristic Adult
N = 3861
Children (<18)
N = 621
p-value2
Age at admission 0.00
    Median (Min, Max) 33 (18, 71) 10 (0, 17)
Age Group 0.00
    <2 0 (0%) 10 (16%)
    2-5 0 (0%) 8 (13%)
    5-12 0 (0%) 20 (32%)
    12-17 0 (0%) 24 (39%)
    18+ 386 (100%) 0 (0%)
Gender 0.75
    Male 166 (43%) 28 (45%)
    Female 220 (57%) 34 (55%)
Patient occupation 0.02
    Healthcare worker 45 (19%) 0 (0%)
    Non-healthcare worker 111 (47%) 21 (68%)
    Unknown 78 (33%) 10 (32%)
Is the patient pregnant? 15 (3.9%) 1 (1.6%) 0.71
Does the patient have any comorbid conditions? 8 (2.1%) 0 (0%) 0.61
Diabetes 1 (0.3%) 0 (0%) 1.00
HIV 3 (0.8%) 0 (0%) 1.00
Chronic pulmonary disease 1 (0.3%) 0 (0%) 1.00
Bleeding 33 (8.5%) 7 (11%) 0.48
Fever 197 (51%) 51 (82%) 0.00
Diarrhoea 142 (37%) 17 (27%) 0.15
Shock 2 (0.5%) 0 (0%) 1.00
Confusion 1 (0.3%) 0 (0%) 1.00
Ebola RDT 1.00
    Oraquick 4 (1.3%) 0 (0%)
    Not done 313 (99%) 49 (100%)
Admission Delay 0.62
    Median (Min, Max) 4.0 (0.0, 34.0) 4.0 (0.0, 39.0)
Ct (lowest) 0.30
    Median (Min, Max) 24 (15, 42) 23 (16, 40)
Result of GeneXpert PCR 0.36
    Positive 322 (99%) 50 (98%)
    Negative 1 (0.3%) 1 (2.0%)
    Indeterminate 1 (0.3%) 0 (0%)
Platelets (x10⁹/L) 0.41
    Median (Min, Max) 168 (27, 385) 106 (88, 164)
Haemoglobin (g/L) 0.40
    Median (Min, Max) 13.30 (9.00, 17.90) 12.00 (10.60, 13.80)
Calcium (mmol/L) US 0.57
    Median (Min, Max) 8.20 (4.00, 10.40) 8.50 (7.50, 9.70)
Hyperkaliemia 5 (1.3%) 2 (3.2%) 0.25
Hypokaliemia 10 (2.6%) 1 (1.6%) 1.00
Renal impairment 41 (11%) 3 (4.8%) 0.16
Rhabdomyolysis 17 (4.4%) 2 (3.2%) 1.00
Severe hypoglycemia 6 (1.6%) 1 (1.6%) 1.00
Oral/orogastric fluids 64 (17%) 13 (21%) 0.40
Antibacterial treatment 326 (84%) 52 (84%) 0.91
Antimalarial treatment 285 (74%) 43 (69%) 0.46
Ebola experimental treatment 170 (44%) 25 (40%) 0.58
Type of Ebola experimental treament 0.37
    None 219 (57%) 37 (60%)
    Remdesivir (GS-5734) 53 (14%) 5 (8.1%)
    Zmapp 7 (1.8%) 1 (1.6%)
    mAb114 64 (17%) 15 (24%)
    REGN3470-3471-3479 43 (11%) 4 (6.5%)
Outcome at discharge 0.48
    Death 126 (33%) 20 (32%)
    Full recovery with sequelae 1 (0.3%) 0 (0%)
    Full recovery without sequelae 216 (56%) 31 (50%)
    Referred to another facility 2 (0.5%) 0 (0%)
    Unknown 41 (11%) 11 (18%)
1 n (%)
2 Wilcoxon rank sum test; Fisher’s exact test; Pearson’s Chi-squared test
Population characteristics among Children by Age Group
Characteristic <2
N = 101
2-5
N = 81
5-12
N = 201
12-17
N = 241
p-value2
Age at admission 0.00
    Median (Min, Max) 1.0 (0.0, 1.9) 3.0 (2.0, 4.0) 8.0 (5.0, 11.0) 15.0 (12.0, 17.0)
Gender 0.15
    Male 6 (60%) 3 (38%) 12 (60%) 7 (29%)
    Female 4 (40%) 5 (63%) 8 (40%) 17 (71%)
Patient occupation 0.45
    Non-healthcare worker 3 (60%) 3 (75%) 10 (83%) 5 (50%)
    Unknown 2 (40%) 1 (25%) 2 (17%) 5 (50%)
Is the patient pregnant? 0 (0%) 0 (0%) 0 (0%) 1 (4.2%) 1.00
Bleeding 0 (0%) 2 (25%) 3 (15%) 2 (8.3%) 0.33
Fever 9 (90%) 8 (100%) 15 (75%) 19 (79%) 0.50
Diarrhoea 2 (20%) 1 (13%) 5 (25%) 9 (38%) 0.55
Ebola RDT
    Not done 8 (100%) 7 (100%) 16 (100%) 18 (100%)
Admission Delay 0.00
    Median (Min, Max) 1 (0, 5) 2 (1, 10) 4 (0, 32) 7 (0, 39)
Ct (lowest) 0.25
    Median (Min, Max) 30 (18, 37) 23 (17, 36) 23 (16, 40) 22 (16, 36)
Result of GeneXpert PCR 0.33
    Positive 9 (90%) 7 (100%) 17 (100%) 17 (100%)
    Negative 1 (10%) 0 (0%) 0 (0%) 0 (0%)
Platelets (x10⁹/L) 0.22
    Median (Min, Max) -- -- 164 (164, 164) 97 (88, 106)
Haemoglobin (g/L) 0.22
    Median (Min, Max) -- -- 10.60 (10.60, 10.60) 12.90 (12.00, 13.80)
Hyperkaliemia 1 (10%) 0 (0%) 1 (5.0%) 0 (0%) 0.47
Hypokaliemia 0 (0%) 0 (0%) 0 (0%) 1 (4.2%) 1.00
Renal impairment 0 (0%) 0 (0%) 0 (0%) 3 (13%) 0.37
Rhabdomyolysis 0 (0%) 0 (0%) 2 (10%) 0 (0%) 0.27
Severe hypoglycemia 0 (0%) 1 (13%) 0 (0%) 0 (0%) 0.13
Oral/orogastric fluids 3 (30%) 1 (13%) 6 (30%) 3 (13%) 0.41
Antibacterial treatment 9 (90%) 7 (88%) 17 (85%) 19 (79%) 0.92
Antimalarial treatment 8 (80%) 6 (75%) 14 (70%) 15 (63%) 0.80
Ebola experimental treatment 4 (40%) 3 (38%) 8 (40%) 10 (42%) 1.00
Type of Ebola experimental treament 0.78
    None 6 (60%) 5 (63%) 12 (60%) 14 (58%)
    Remdesivir (GS-5734) 0 (0%) 0 (0%) 1 (5.0%) 4 (17%)
    Zmapp 0 (0%) 0 (0%) 0 (0%) 1 (4.2%)
    mAb114 3 (30%) 2 (25%) 5 (25%) 5 (21%)
    REGN3470-3471-3479 1 (10%) 1 (13%) 2 (10%) 0 (0%)
Outcome at discharge 0.09
    Death 0 (0%) 2 (25%) 6 (30%) 12 (50%)
    Full recovery without sequelae 6 (60%) 5 (63%) 11 (55%) 9 (38%)
    Unknown 4 (40%) 1 (13%) 3 (15%) 3 (13%)
1 n (%)
2 Kruskal-Wallis rank sum test; Fisher’s exact test; NA
Population characteristics among Children by Outcome
Characteristic Deceased
N = 201
Recovered
N = 311
p-value2
Age at admission 0.01
    Median (Min, Max) 13.5 (3.0, 17.0) 7.0 (0.0, 17.0)
Age Group 0.07
    <2 0 (0%) 6 (19%)
    2-5 2 (10%) 5 (16%)
    5-12 6 (30%) 11 (35%)
    12-17 12 (60%) 9 (29%)
Gender 0.47
    Male 7 (35%) 14 (45%)
    Female 13 (65%) 17 (55%)
Patient occupation 0.36
    Non-healthcare worker 4 (80%) 9 (53%)
    Unknown 1 (20%) 8 (47%)
Is the patient pregnant? 0 (0%) 1 (3.2%) 1.00
Bleeding 4 (20%) 2 (6.5%) 0.19
Fever 17 (85%) 27 (87%) 1.00
Diarrhoea 7 (35%) 7 (23%) 0.33
Ebola RDT
    Not done 17 (100%) 25 (100%)
Admission Delay 0.00
    Median (Min, Max) 7 (1, 39) 2 (0, 32)
Ct (lowest) 0.00
    Median (Min, Max) 19 (16, 29) 27 (19, 40)
Result of GeneXpert PCR 1.00
    Positive 17 (100%) 24 (96%)
    Negative 0 (0%) 1 (4.0%)
Platelets (x10⁹/L) 0.67
    Median (Min, Max) 135 (106, 164) 88 (88, 88)
Haemoglobin (g/L) 1.00
    Median (Min, Max) 12.20 (10.60, 13.80) 12.00 (12.00, 12.00)
Hyperkaliemia 1 (5.0%) 1 (3.2%) 1.00
Hypokaliemia 0 (0%) 1 (3.2%) 1.00
Renal impairment 3 (15%) 0 (0%) 0.05
Rhabdomyolysis 2 (10%) 0 (0%) 0.15
Severe hypoglycemia 0 (0%) 1 (3.2%) 1.00
Oral/orogastric fluids 2 (10%) 9 (29%) 0.17
Antibacterial treatment 17 (85%) 26 (84%) 1.00
Antimalarial treatment 13 (65%) 21 (68%) 0.84
Ebola experimental treatment 10 (50%) 10 (32%) 0.21
Type of Ebola experimental treament 0.02
    mAb114 3 (15%) 7 (23%)
    None 10 (50%) 21 (68%)
    REGN3470-3471-3479 1 (5.0%) 3 (9.7%)
    Remdesivir (GS-5734) 5 (25%) 0 (0%)
    Zmapp 1 (5.0%) 0 (0%)
1 n (%)
2 Wilcoxon rank sum test; Fisher’s exact test; Pearson’s Chi-squared test; NA; Wilcoxon rank sum exact test
  • Eleven participants with unknown outcome at discharge.
Population characteristics among Children by Sex
Characteristic Male
N = 281
Female
N = 341
p-value2
Age at admission 0.07
    Median (Min, Max) 7.5 (0.0, 17.0) 12.0 (0.0, 17.0)
Age Group 0.15
    <2 6 (21%) 4 (12%)
    2-5 3 (11%) 5 (15%)
    5-12 12 (43%) 8 (24%)
    12-17 7 (25%) 17 (50%)
Patient occupation 0.01
    Non-healthcare worker 13 (93%) 8 (47%)
    Unknown 1 (7.1%) 9 (53%)
Is the patient pregnant? 0 (0%) 1 (2.9%) 1.00
Bleeding 2 (7.1%) 5 (15%) 0.44
Fever 21 (75%) 30 (88%) 0.20
Diarrhoea 9 (32%) 8 (24%) 0.45
Ebola RDT
    Not done 22 (100%) 27 (100%)
Admission Delay 0.86
    Median (Min, Max) 4 (0, 28) 4 (0, 39)
Ct (lowest) 0.72
    Median (Min, Max) 24 (16, 40) 23 (16, 40)
Result of GeneXpert PCR 1.00
    Positive 24 (100%) 26 (96%)
    Negative 0 (0%) 1 (3.7%)
Platelets (x10⁹/L) 0.67
    Median (Min, Max) 164 (164, 164) 97 (88, 106)
Haemoglobin (g/L) 0.67
    Median (Min, Max) 10.60 (10.60, 10.60) 12.90 (12.00, 13.80)
Hyperkaliemia 2 (7.1%) 0 (0%) 0.20
Hypokaliemia 0 (0%) 1 (2.9%) 1.00
Renal impairment 1 (3.6%) 2 (5.9%) 1.00
Rhabdomyolysis 2 (7.1%) 0 (0%) 0.20
Severe hypoglycemia 0 (0%) 1 (2.9%) 1.00
Oral/orogastric fluids 7 (25%) 6 (18%) 0.48
Antibacterial treatment 24 (86%) 28 (82%) 1.00
Antimalarial treatment 18 (64%) 25 (74%) 0.43
Ebola experimental treatment 9 (32%) 16 (47%) 0.23
Type of Ebola experimental treament 0.39
    None 19 (68%) 18 (53%)
    Remdesivir (GS-5734) 3 (11%) 2 (5.9%)
    Zmapp 0 (0%) 1 (2.9%)
    mAb114 4 (14%) 11 (32%)
    REGN3470-3471-3479 2 (7.1%) 2 (5.9%)
Outcome at discharge 0.34
    Death 7 (25%) 13 (38%)
    Full recovery without sequelae 14 (50%) 17 (50%)
    Unknown 7 (25%) 4 (12%)
1 n (%)
2 Wilcoxon rank sum test; Fisher’s exact test; Pearson’s Chi-squared test; NA; Wilcoxon rank sum exact test

Sampling

Cases Description

Patient Outcomes by Admission Delay

  • Deceased patients had a median admission delay of 7 days (range 1-39)
  • Recovered patients had a median admission delay of 2 days (range 1-5)

Ct kinetics

  • A linear mixed-effects model with random intercepts per participant showed that Ct values significantly increased over time (β = 0.25, p < 0.001), consistent with viral load decline.
  • Participants who died had markedly lower baseline Ct values compared to recovered individuals (β = −8.65, p < 0.001), indicating higher initial viral loads.
  • The interaction between time and outcome was not significant (p = 0.60), suggesting similar Ct kinetics across outcomes.

\[ Ct_{ij} = \beta_0 + \beta_1 (\text{Time from Onset}_{ij}) + \beta_2 (\text{Outcome}_i) + \beta_3 (\text{Time from Onset} \times \text{Outcome}_i) + u_i + \epsilon_{ij} \]

  • (Ct_{ij}): Ct value for participant i at time j
  • (_0): intercept (baseline Ct for recovered)
  • (_1): daily Ct change among recovered
  • (_2): baseline difference (Death vs Recovered)
  • (_3): interaction (difference in Ct trajectory)
  • (u_i): random intercept
  • (_{ij}): residual error

Cases and CFR

Treatments and complications

These complications are inferred from laboratory results :

  • Renal impairment: Creatinine (mg/dL)≥1.1
  • Hyperkaliemia: Potassium (mmol/L)>5.5
  • Hypokaliemia: Potassium (mmol/L)<3.5
  • Rhabdomyolysis: Creatinine kinase (U/L)>1000
  • Severe hypoglycemia: Glucose (mg/dL) <60
  • Severe thrombocytopenia: Platelets (x10⁹/L) <50

Analyses

Approach

flow ImmuneMod Immune modulation DelDirect Deleterious direct effect of virus ImmuneMod->DelDirect +/- ViralLoad Viral load ViralLoad->DelDirect + OrganFail Organ failure DelDirect->OrganFail + Death Death OrganFail->Death + PreExist Pre-existing comorbidity PreExist->OrganFail + Age Age Age->PreExist +/- Sex Sex Sex->PreExist DelayedPres Delayed presentation Sex->DelayedPres Nutrition Nutrition Nutrition->PreExist + DelayedPres->ViralLoad + Vaccination Vaccination Vaccination->ViralLoad - Antiviral Antiviral therapy Antiviral->ViralLoad - Hypoperf Hypoperfusion / shock Hypoperf->OrganFail + Dehydration Dehydration Dehydration->Hypoperf + MetElect Metabolic / electrolyte derangement Dehydration->MetElect + MetElect->OrganFail + Hypoxa Hypoxaemia Hypoxa->OrganFail + Anemia Anaemia Anemia->Hypoxa + SecInf Secondary infection SecInf->OrganFail + SecInf->Hypoxa + Bleeding Bleeding Bleeding->Anemia + ORS ORS ORS->Dehydration - IVfluid IV fluid IVfluid->Dehydration - IVfluid->MetElect - Diarrhoea Diarrhoea Diarrhoea->Dehydration +
  • This Directed Acyclic Graphs (DAG) illustrates hypothesized causal relationships underlying EVD pathophysiology and clinical outcomes.
workflow A 1. Data cleaning and wrangling B 2. Univariate model screening • Identify sparse variables • Exclude predictors causing quasi-complete separation A->B C 3. Collinearity assessment • Variance Inflation Factor (VIF) • GVIF_scaled ≤ 1.68 B->C D 4. LASSO regression • Shrinks weak predictors • Retains strongest associations C->D E 5. Multivariable logistic regression • Include LASSO-selected predictors D->E F OR from multivariable model E->F G Adjusted RR (Poisson) E->G H Raw RR for binary predictors E->H

Ct threshold to predict participant outcome

  • ROC analyses were performed to determine the optimal Ct threshold to predict participant outcome.
  • With an area under the curve (AUC) of 0.87, ROC analyses evaluated the optimal Ct threshold cut-off at 21.35 for predicting patients outcome (sensitivity 79%, specificity 77%).

Independent Predictors of EVD Outcome

  • Multivariable Poisson regression with robust standard errors was used to estimate adjusted risk ratios (aRR) and 95% confidence intervals.
Variable Relative Risk (95% CI) Direction
CT at Admission 0.85 (0.74-0.98)
Chest Pain 1.85 (0.63-5.4) ↔︎
Desorientation 1.83 (0.76-4.41) ↔︎
Difficulty breathing 1.07 (0.48-2.38) ↔︎
Myalgia / Body Pain 2.02 (1.09-3.71)
Nausea/Vomiting 1.34 (0.36-4.94) ↔︎

Survival Analyses

  • We used a Weibull proportional hazards model to estimate survival probabilities over time.

  • Forest plot showing relative effects of covariates on survival time estimated from a Weibull proportional hazards model. HR > 1 indicates shorter survival (faster occurrence of the event), HR < 1 indicates longer survival. Error bars represent 95% confidence intervals.

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